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Candida albicans is a fungal pathobiont colonizing mucosal surfaces of the human body, including the oral cavity. Under certain predisposing conditions, C. albicans invades mucosal tissues activating EGFR-MAPK signalling pathways in epithelial cells via the action of its peptide toxin candidalysin. However, our knowledge of the epithelial mechanisms involved during C. albicans colonization is rudimentary. Here, we describe the role of the transcription factor early growth response protein 1 (EGR1) in human oral epithelial cells (OECs) in response to C. albicans. EGR1 expression increases in OECs when exposed to C. albicans independently of fungal viability, morphology, or candidalysin release, suggesting EGR1 is involved in the fundamental recognition of C. albicans, rather than in response to invasion or “pathogenesis.” Upregulation of EGR1 is mediated by EGFR via Raf1, ERK1/2, and NF-κB signalling but not PI3K/mTOR signalling. Notably, EGR1 mRNA silencing impacts on anti-C. albicans immunity, reducing GM-CSF, IL-1α and IL-1β release, and increasing IL-6 and IL-8 production. These findings identify an important role for EGR1 in priming epithelial cells to respond to subsequent invasive infection by C. albicans and elucidate the regulation circuit of this transcription factor after contact.

Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt. Enteroids generated from the developing human intestine grown in standard culture conditions, which contain EGF, are dominated by stem and progenitor cells and feature little differentiation and no spatial organization. Our results demonstrate that EREG can replace EGF in vitro, and EREG leads to spatially resolved enteroids that feature budded and proliferative crypt domains and a differentiated villus-like central lumen. Multiomic (transcriptome plus epigenome) profiling of native crypts, EGF-grown enteroids, and EREG-grown enteroids showed that EGF enteroids have an altered chromatin landscape that is dependent on EGF concentration, downregulate the master intestinal transcription factor CDX2, and ectopically express stomach genes, a phenomenon that is reversible. This is in contrast to EREG-grown enteroids, which remain intestine like in culture. Thus, EREG creates a homeostatic intestinal niche in vitro, enabling interrogation of stem cell function, cellular differentiation, and disease modeling.

Abstract The initial exposure to pathogens and commensals confers innate immune cells the capacity to respond distinctively upon a second stimulus. This training capacity might play key functions in developing an adequate innate immune response to the continuous exposure to bacteria. However, the mechanisms involved in induction of trained immunity by commensals remain mostly unexplored. A. muciniphila represents an attractive candidate to study the promotion of these long-term responses. Here, we show that priming of macrophages with live A. muciniphila enhances bacterial intracellular survival and decreases the release of pro- and anti-inflammatory signals, lowering the production of TNF and IL-10. Global transcriptional analysis of macrophages after a secondary exposure to the bacteria showed the transcriptional rearrangement underpinning the phenotype observed compared to acutely exposed cells, with the increased expression of genes related to phagocytic capacity and those involved in the metabolic adjustment conducing to innate immune training. Accordingly, key genes related to bacterial killing and pro-inflammatory pathways were downregulated. These data demonstrate the importance of specific bacterial members in the modulation of local long-term innate immune responses, broadening our knowledge of the association between gut microbiome commensals and trained immunity as well as the anti-inflammatory probiotic potential of A. muciniphila.

Metabolic differences between Candida species are uncovered using the BioFung database alongside genomic and metabolic analysis.

The paper introduces the Oil-Slick Hub (OSH), a computational platform to facilitate the data visualization of a large database of petroleum signatures observed on the surface of the ocean with synthetic aperture radar (SAR) measurements. This Internet platform offers an information search and retrieval system of a database resulting from >20 years of scientific projects that interpreted ~15 thousand offshore mineral oil “slicks”: natural oil “seeps” versus operational oil “spills”. Such a Digital Mega-Collection Database consists of satellite images and oil-slick polygons identified in the Gulf of Mexico (GMex) and the Brazilian Continental Margin (BCM). A series of attributes describing the interpreted slicks are also included, along with technical reports and scientific papers. Two experiments illustrate the use of the OSH to facilitate the selection of data subsets from the mega collection (GMex variables and BCM samples), in which artificial intelligence techniques—machine learning (ML)—classify slicks into seeps or spills. The GMex variable dataset was analyzed with simple linear discriminant analyses (LDAs), and a three-fold accuracy performance pattern was observed: (i) the least accurate subset (~65%) solely used acquisition aspects (e.g., acquisition beam mode, date, and time, satellite name, etc.); (ii) the best results (>90%) were achieved with the inclusion of location attributes (i.e., latitude, longitude, and bathymetry); and (iii) moderate performances (~70%) were reached using only morphological information (e.g., area, perimeter, perimeter to area ratio, etc.). The BCM sample dataset was analyzed with six traditional ML methods, namely naive Bayes (NB), K-nearest neighbors (KNN), decision trees (DT), random forests (RF), support vector machines (SVM), and artificial neural networks (ANN), and the most effective algorithms per sample subsets were: (i) RF (86.8%) for Campos, Santos, and Ceará Basins; (ii) NB (87.2%) for Campos with Santos Basins; (iii) SVM (86.9%) for Campos with Ceará Basins; and (iv) SVM (87.8%) for only Campos Basin. The OSH can assist in different concerns (general public, social, economic, political, ecological, and scientific) related to petroleum exploration and production activities, serving as an important aid in discovering new offshore exploratory frontiers, avoiding legal penalties on oil-seep events, supporting oceanic monitoring systems, and providing valuable information to environmental studies.

The tectonic affinity and origins of the Jurassic, siliciclastic San Cayetano and Constancia formations exposed in western and central Cuba in the Caribbean region remain debated. The scarcity of modern geochronologic studies on these Cuban units hampers both sedimentary provenance and palinspastic reconstructions, resulting in Caribbean models that tend to oversimplify the formation of Cuba and correlate the Jurassic strata to various regions such as North America, South America, the Yucatán margin, or the conceptual Caribeana domain. Using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), we conducted a detailed detrital zircon (DZ) U-Pb provenance study of these Cuban siliciclastic strata that provides critical insights into understanding the formation of Cuba during the Early Jurassic rifting stages of Pangea. Results from 19 San Cayetano Formation samples show a dominant Oaxaquia (ca. 1 Ga) and Chiapas batholith (ca. 250 Ma) signature, while six Constancia samples display variable ca. 1 Ga and ca. 250 Ma grains. The Lower Cretaceous Polier Formation and the Paleocene Moncada Formation also display the same ca. 1 Ga and ca. 250 Ma signatures. After comparing these Cuban data with data from other regional DZ studies, we propose that that the San Cayetano and Constancia formations are correlative to the Todos Santos Formation located in the southwestern Yucatán region of Mexico. These Cuban units were predominantly deposited adjacent to the Chiapas batholith during the Early Jurassic in northwest-southeast-trending basins created by Pangean rifting. They were eventually sheared during eastward migration of the Caribbean plate and transported northward until they collided with the North American continent in the Paleogene. This DZ study provides new constraints on the tectonic provenance of western and central Cuba and improves plate tectonic reconstructions of the Caribbean. [ABSTRACT FROM AUTHOR]